Potential Agents Research Articles

Jing-Yin-Gu-Biao formula protects mice from postinfluenza Staphylococcus aureus infection by ameliorating acute lung injury and improving hypercoagulable state via inhibiting NETosis

BackgroundJing-Yin-Gu-Biao formula (JYGBF) is a Chinese medicine derived from Yupingfeng power, Huoxiangzhengqi powder and Yinqiao powder, and has been widely used to treat acute respiratory infections. This study aims to observe the effects of JYGBF against postinfluenza Staphylococcus aureus (S. aureus) infection.Purpose and study designA mouse model of secondary S. aureus infection following PR8 infection was established to evaluate the protective effects of JYGBF against postinfluenza Staphylococcus aureus (S. aureus) infection and related mechanisms were validated in vivo and in vitro.ResultsThe administration of JYGBF significantly ameliorated acute lung injury (ALI) and inhibited overactivated inflammatory response (MIP-2, IL-6, etc.) in mice with postinfluenza S. aureus infection. Single cell RNA-sequencing (scRNA-seq) data indicated that neutrophils had the highest cytokine score in lungs and JYGBF inhibited neutrophil chemotaxis, reactive oxygen species (ROS) biosynthesis and ERK1/2 cascades in neutrophils. Meanwhile, JYGBF inhibited the formation of neutrophil extracellular traps (NETs) in lungs, which is characterized by the production of ROS, peptidyl arginine deiminase 4 (PAD4), citrullinated histone H3 (CitH3), myeloperoxidase (MPO), neutrophil elastase (NE), S100A8/A9 and MPO-CitH3 colocalization. Moreover, JYGBF decreased platelet counts and the expression of its activated markers (CD62P and αIIbβ3) accompanied by the drop of fibrinogen (FIB) and fibrin degradation product (FDP), accounting for alleviating hypercoagulable state. JYGBF inhibited ERK1/2 phosphorylation in neutrophils and in lungs of infected mice. Acacetin, a critical compound from JYGBF, inhibited NET formation via downregulating ERK/ROS axis.ConclusionsThese results indicated that JYGBF inhibited NET formation and overactivated inflammatory response by suppressing ERK/ROS axis in neutrophils, thereby mitigating ALI and improving the hypercoagulable state during postinfluenza S. aureus infection. JYGBF could be considered a potent therapeutic agent for the prevention and treatment of postinfluenza bacterial infection.

Phytochemical analysis and anticancer potential of Iraqi Allium sativum on colon cancer cells

Allium sativum has been cultivated in different areas around the world and has been used as a food, condiment. Many sources mention Allium sativum as a potential treatment for different ailments. The Current study aimed to assess the anticarcinogenic and antitumor properties of Allium sativum and identify of the major phytochemicals present in Iraqi species. Specific and general tests were carried out for the qualitative analysis of different natural components present in the plant extract in addition to the assessment of the possible antitumor activity of Allium sativum by detecting the dose-response effect of the methanol extract. Serial extract concentrations were tested on a colon cancer cell line to determine the dose-response effect. The anticancer effects after 48 hours of exposure showed a significant inhibition rate in a dose-dependent manner on cancer cell growth. The IC50 value of the extract was found to be 35.13 µg/mL. The inhibition rates at various concentrations were as follows: at 200 µg/mL, the inhibition was 90.9 ± 0.03 %, at 100 µg/mL, it was 68.1 ± 0.05 %, at 50 µg/mL, the inhibition was 52.7 ± 0.09 %, at 25 µg/mL, it was 49.54 ± 0.03 %, at 12.5 µg/mL, it was 36.3 ± 0.05 % and at 6.25 µg/mL, the inhibition was 36.2 ± 0.05 %. Phytochemical analysis revealed the presence of several bioactive secondary metabolites in the methanol extract, including alkaloids, saponins, steroids, carbohydrates, flavonoids, terpenoids, anthraquinones and cardiac glycosides. These compounds are likely supporting the potential of Allium sativum as a natural anticancer treatment.

Azaphenothiazine Conjugates: A New Class of Antimicrobial Compounds

ABSTRACTAlthough phenothiazines have been widely explored in medicinal chemistry for over a century, little attention has been paid to their pyridine analogs, azaphenothiazines. This article reports the first synthesis, characterization, and antimicrobial evaluation of S‐oxide analogs of N‐aminoalkylated azaphenothiazines as antibacterials and antifungals. The optimized synthetic protocol enabled the production of the desired azaphenothiazine sulfoxides 12a–e and sulfonyls 14a–e, respectively. In addition to the x‐ray crystal structure of azaphenothiazine sulfoxide intermediate 10, each target compound was characterized using spectroscopy techniques. All of these were investigated in vitro for antibacterial and antifungal activity against several strains of bacteria and fungi. Biological assays revealed selective antibacterial activity, with sulfoxides (12a–e) exhibiting broad inhibition and sulfones (14a–e) showing selectivity toward gram‐negative bacteria. Compound 12c demonstrated fourfold higher potency against Escherichia coli than the reference drug. In antifungal studies, compound 14c showed the highest activity (MIC 1.2 µg/mL against Candida albicans). Our in silico evaluations utilized molecular dynamic (MD) and docking studies for active‐site binding simulations, revealing favorable drug‐like properties and pharmacokinetics. Finally, toxicology assays determined all synthesized analogs to be non‐toxic to kidney and hepatic tissues. This report highlights the newly described S‐oxide azaphenothiazine conjugates and their potential as potent antimicrobial agents.

Inhibition of Retinoblastoma Cell Growth by Boswellic Acid Through Activation of the Suppressing Nuclear Factor—κB Activation

Background and Objectives: Despite the development of treatment methods and the emergence of alternative new approaches in recent years, the visual prognosis of retinoblastoma contains deficiencies and this situation increases the need for the development of new treatment approaches. The cytotoxic and apoptosis-inducing effects of the combination of boswellic acid (BA), which has been determined to have significant potential in preclinical and clinical studies of various diseases, and Cisplatin (Cis), a potent chemotherapy agent, were investigated on the human retinoblastoma cell line (Y79). Materials and Methods: The cytotoxic effect of BA and Cis on Y79 cells was determined by the water soluble tetrazolium-1 (WST-1) test, the apoptotic rate of the cells was determined by annexin V staining, and the gene expressions of Protein53 (p53), Caspase-3 and Nuclear factor kappa B (NF-κB), which play an important role in apoptosis, were determined by RT-qPCR analysis. Interleukin 1-beta (IL1-β), tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ) levels were analyzed in cell lysates obtained from the experimental groups. Results: The combination of BA and Cis selectively inhibited the growth of Y79 cells and modulated NF-κB signaling, potentially through post-translational regulatory mechanisms. Moreover, it induced apoptosis by increasing p53 and Caspase-3 expressions, confirming its pro-apoptotic effects. Additionally, the combination treatment was associated with a reduction in inflammatory cytokine levels (TNF-α, IL1-β), suggesting a potential regulatory effect on inflammation-related pathways rather than direct inhibition of NF-κB activation. Conclusions: These findings suggest that BA combined with Cis inhibits Y79 retinoblastoma cell growth by inducing apoptosis and modulating NF-κB signaling. While NF-κB mRNA levels increased, reduced inflammatory cytokines and enhanced apoptosis suggest potential post-translational regulation. Further studies are needed to confirm NF-κB protein-level effects and in vivo efficacy.

Development of a Novel 11-Gene Signature Related to Immune Subtypes for Fibromyalgia.

The purpose of this study was to identify molecular subtypes and hub genes in fibromyalgia [FM] based on immune-related genes [IRGs]. FM is a chronic disease featuring widespread pain, and the immune system may be involved in the FM progression. The objectives of this study are as follows: 1] To identify the molecular subtypes of FM based on IRGs. 2] To screen and validate the hub genes in FM. 3] To predict the transcription factor [TF] targeting hub genes and 4] To evaluate the correlation between immune cell infiltration, hallmark pathways, and hub genes. Two FM datasets were acquired from the Gene Expression Omnibus [GEO] database. IRGs were collected from the ImmPort database. Molecular subtypes of FM were identified using the "ConsensusClusterPlus" package. IRGs score and differentially expressed genes [DEGs] between different FM subtypes and control samples were obtained using "GSVA" and "limma" packages. Key module genes related to FM subtypes were identified using the "WGCNA" package. Hub genes were screened and verified using "glmnet" and "pROC" packages. TF-hub gene regulatory network was constructed by Cytoscape software. The correlation between immune cells, hallmark pathways, and hub genes was analyzed by the Spearman method. Finally, the DSigDB database was used to obtain associations between characterized genes and drugs, and the expression of key genes was verified using qRT-PCR. FM samples were classified into two subtypes, and the IRGs score of the C2 subtype was lower than that of the C1 subtype. Then, 184 module genes were obtained and mainly enriched in immune-related pathways. Next, 11 hub genes [TSPAN16, RILPL2, RASSF5, PGAP2, PADI2, NACC1, LRRC25, ITGAD, HIPK1, ATP6V0D1, AP1M2] were screened with good diagnostic performance. Besides, 45 TFs targeting hub genes were predicted. Most hub genes were negatively associated with CD4/CD8 T cells while positively correlated with macrophages, mast cell, monocyte, and neutrophil, as well as inflammatory response, angiogenesis pathways, etc. Molecular docking suggests that chloroquine and L-citrulline may be potent agents for the treatment of NACC1 and PADI2. RILPL2 and ITGAD were significantly differentially expressed in control and FM group mouse models. This study identified two subtypes and 11 hub genes of FM based on IRGs, providing a reference for the clinical diagnosis of FM.

MDA-9/Syntenin as a therapeutic cancer metastasis target: current molecular and preclinical understanding.

Metastasis is a principal cause of patient morbidity and death from solid cancers with current therapies being inadequate. Detailed genomic analyses document mutational differences between the initial tumor and metastatic clones, posing a challenge to current targeted therapies, which focus predominantly on the phenotype of primary tumors. Considering the diverse signaling cascades and numerous compensatory pathways in metastasis, designing broad-spectrum anti-metastatic therapies remains challenging. Although significant anti-cancer activity is evident in specific patients with advanced cancers and metastases treated with single or combination immunotherapies, there are limitations, i.e. toxicity, immune inhibitory 'cold' tumors and the tumor microenvironment (TME), and intra- and intertumoral heterogeneity. Accordingly, multidisciplinary strategies are required to attack metastases and the TME to obtain optimal therapeutic responses. To create potent anti-metastatic agents, defining critical genes/proteins and drugs controlling discrete steps in the metastatic cascade are mandatory. Melanoma differentiation-associated gene-9 (MDA-9), Syndecan Binding Protein (SDCBP) or Syntenin (MDA-9/Syntenin) is robustly expressed and serves essential roles in cancer disease progression through protein-protein interactions with additional metastasis-associated molecules and pathways. The importance of MDA-9/Syntenin in the metastatic process is now established and first-in-class inhibitory molecules look promising with some moving toward clinical evaluation.

Ugi-Trimethylsilylazide-Mediated Efficient Synthesis of Tetrazole-Adamantane Hybrids as Anticancer Agents

Aim: This study aimed to synthesize a series of tetrazole-adamantane hybrids using the Ugi-tetrazole four-component reaction and evaluate their anticancer potential. Background: The search for new, potent, and less toxic anticancer agents has driven the exploration of innovative molecular designs. The Ugi-tetrazole four-component reaction offers an efficient approach to synthesizing tetrazole-containing compounds, which possess bioisosteric properties, combined with the hydrophobic characteristics of adamantane. Methods: Tetrazole-adamantane hybrids (5a-p) were synthesized by reacting an aldehyde, 1- adamantylamine, substituted isocyanides, and trimethylsilylazide in methanol. The compounds were characterized using mass spectrometry (MS), infrared (IR), and nuclear magnetic resonance (NMR) spectroscopy. The anticancer activity was assessed using the National Cancer Institute's 60 human tumor cell line panel (NCI-60) and MTT assays. Results: A series of tetrazole-adamantane hybrids (5a-p) were successfully synthesized. Compounds 5e, 5g, 5k, and 5l exhibited significant cytotoxicity against breast (MDA-MB-231, IC50 = 2.1 μM), lung (NCI-H460, IC50 = 1.8 μM), and leukemia (K562, IC50 = 3.0 μM) cell lines. Conclusion: The Ugi-tetrazole four-component reaction provided a reliable route for synthesizing tetrazole-adamantane hybrids (5a-p) with promising anticancer activity. These hybrids showed potential as novel anticancer agents for treating breast, lung, and leukemia cancers. Further optimization and in vivo studies are warranted to explore their therapeutic potential. conclusion: The study successfully synthesized a novel series of tetrazole-adamantane hybrids using the Ugi-Tetrazole four-component reaction (UT-4CR). The compounds demonstrated promising anticancer activity, indicating their potential as candidates for further development as anticancer therapeutics. The incorporation of tetrazole and adamantane in a single molecular entity may offer an effective strategy for generating novel anticancer agents with desirable bioactivity profiles.

Mitigating Doxorubicin-Induced Cardiotoxicity and Enhancing Anti-Tumor Efficacy with a Metformin-Integrated Self-Assembled Nanomedicine.

Doxorubicin (Dox) is a potent chemotherapeutic agent commonly used in cancer treatment. However, cardiotoxicity severely limited its clinical application. To address this challenge, a novel self-assembled nanomedicine platform, PMDDH, is developed for the co-delivery of Dox and metformin, an antidiabetic drug with cardioprotective and anti-tumor properties. PMDDH integrates metformin into a polyethyleneimine-based bioactive excipient (PMet), with Dox intercalated into double-stranded DNA and a hyaluronic acid (HA) coating to enhance tumor targeting. The PMDDH significantly improves the pharmacokinetics and tumor-targeting capabilities of Dox, while metformin enhances the drug's anti-tumor activity by downregulating programmed cell death ligand 1 (PD-L1) and activating the AMP-activated protein kinase (AMPK) signaling pathway. Additionally, the DNA component stimulates the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which synergizes with Dox-induced immunogenic cell death (ICD) to promote a robust anti-tumor immune response. PMDDH markedly reduces Dox-induced cardiotoxicity by preserving mitochondrial function, reducing reactive oxygen species (ROS) production, and inducing protective autophagy in cardiomyocytes. These findings position PMDDH as a promising dual-function nanomedicine that enhances the anti-tumor efficacy of Dox while minimizing its systemic toxicity, offering a safer and more effective alternative for cancer therapy.

Polylactic-Co-Glycolic Acid/Alginate/Neem Oil-Reduced Graphene Oxide as a pH-Sensitive Nanocarrier for Hesperidin Drug Delivery: Antimicrobial and Acute Otitis Media Assessments

Background/Objectives: Hesperidin (HSP) is a potent phytochemical antioxidant and anti-inflammatory agent that protects against otitis media. However, due to its low solubility and bioavailability, a suitable delivery method is needed to overcome these problems. A hydrogel is a promising nanocarrier for controlled drug delivery in response to external stimuli, such as pH variations. Methods: Graphene oxide (GO)-based nanocarriers that encapsulate hesperidin (HSP) were further coated with a polylactic-co-glycolic acid/alginate (PLGA-Alg) hydrogel before being integrated into a green neem oil (N.O.) double emulsion to produce a synergistic effect and then characterized by different assays. Results: The nanocarriers exhibited a substantial particle size (168 ± 0.32 nm), with high encapsulation (89.86 ± 0.23%) and a zeta potential of 37 ± 0.43 mV. In vitro release studies conducted over 96 h indicated a sustained HSP release of 82% at pH 5.4 and 65% at pH 7.4. The GO-HSP-loaded neem oil double emulsion formulation exhibits substantial antibacterial activity, as evidenced by inhibition zones of 39 ± 0.02 mm against Staphylococcus epidermidis, and considerable antifungal activity against Candida albicans, with an inhibition zone of 43 ± 0.13 mm, along with biofilm inhibition activity. The formulation demonstrated antioxidant activity (5.21 µg/mL) and increased cell viability (90–95%) while maintaining low cytotoxicity in HSE-2 cells. A histopathological analysis confirmed that treatment with the nanocarriers reduced the levels of pro-inflammatory cytokines (IL-1β, TNF-α, TLR4, IL-6) and raised the levels of antioxidant markers (Nrf-2, SOD) in an in vivo rat model of otitis media. Conclusions: GO-based nanocarriers integrated into a neem oil double emulsion and coated with PLGA-Alg hydrogel deliver hesperidin with sustained release and enhanced antibacterial, antifungal, and antioxidant properties. This formulation may be used to treat otitis media and other oxidative stress diseases.

Bisboronic Ester-Enabled Redox-Targeted Cancer Therapy: A Cascade ROS Consumption Approach for Efficient Elimination of Cancer Cells.

Elevated levels of reactive oxygen species (ROS) in cancer cells, arising from their altered metabolism, represent a distinctive therapeutic target. Here, we introduce the first example of bisboronic esters as potent agents for rapidly disrupting redox homeostasis, selectively inducing oxidative stress to eliminate cancer cells. Structure-activity relationship studies revealed that both the electronic and steric factors significantly influence their cytotoxicity, with the most effective compounds achieving IC50 values as low as 0.63 μM. Confocal imaging confirmed the rapid intracellular depletion of ROS, leading to a severe metabolic imbalance and efficient cancer cell death. This study highlights the potential of boronate-based therapeutics for redox-targeted cancer therapy, which may provide a promising foundation for the development of innovative anticancer strategies.

Optimisation of the in vitro liquid culture protocol for Heterorhabditis bacteriophora

Summary Heterorhabditis bacteriophora is an entomopathogenic nematode that maintains a symbiotic relationship with Photorhabdus bacteria, and is a potent biocontrol agent against agricultural insect pests. The mass culture of these nematodes is a critical requirement for their use in commercial biocontrol application. In vitro liquid culture methods have been used successfully to mass produce H. bacteriophora, in both shake flasks and bioreactors. Although shake flask culture methods have achieved high yields, optimisation of in vitro liquid culture techniques for H. bacteriophora is essential for achieving high yields, shortened production time, and cost-effective production. Amendments to the culture medium (CM), such as trehalose powder and dimethyl sulfoxide (DMSO), showed no significant differences in yield from the control. To improve oxygen circulation in flasks the shaker rotational speed was increased from 140 rpm to 160 rpm. There were no significant differences in yield between the two rotational speeds. Additionally, this study highlights the issue of a second generation of nematodes in the CM, as unfertilised adults negatively impact on yields of infective juveniles and batch quality. Reducing the protein sources resulted in an increase in yield. Alternative yeast sources, the most expensive ingredient in the CM, were also compared, with 1451MG having a significantly higher yield compared to the standard laboratory grade yeast used in the culture media.

Recent Developments in the Synthesis of Benzothiazoles and their Anti-cancer Mechanistic Discoveries.

Benzothiazole derivatives have garnered considerable attention owing to their versatile chemical scaffold and remarkable biological activities. The article provides an in-depth analysis of the diverse structural modifications and strategies employed to enhance the anticancer potential of these compounds from the period of 2020 to 2024. It discusses the role of structure-activity relationships (SAR) and computational approaches in optimizing benzothiazole derivatives for selective and effective cancer treatment.

Tacrolimus‐Related Neurotoxicity of the Pons in Children: Review of the Literature and a Case Report

ABSTRACTIntroductionTacrolimus is a potent immunosuppressive agent effective in preventing solid organ transplant rejection. It is widely used following allogeneic liver, kidney, heart, and bone marrow transplantation. Tacrolimus‐related neurotoxicity, which can present in up to one‐third of patients, manifests with a broad clinical spectrum. Neuroradiological features are classically reported as bilateral and symmetrical lesions involving the parietal and occipital lobes, similar to posterior reversible encephalopathy syndrome. Tacrolimus‐related toxicity can also affect other parts of the brain, including the brainstem, although isolated brainstem involvement is rare.MethodsThis report describes a patient who had tacrolimus‐related neurotoxicity with an isolated brainstem lesion in which symptoms resolved with only a brief hold of the tacrolimus. A literature review identified four other pediatric patients who had tacrolimus‐associated neurotoxicity with isolated brainstem involvement.DiscussionTacrolimus‐associated neurotoxicity with pontine lesions in children is rare. In previously reported patients, tacrolimus was discontinued and neurological symptoms resolved. Our patient developed tacrolimus‐associated clinical changes and pontine lesions that improved following a brief hold of the tacrolimus treatment. This girl highlights tacrolimus‐associated neurotoxicity isolated to the brainstem in pediatric patients and demonstrates that tacrolimus may be safely restarted with careful monitoring and follow‐up.

An Investigation into Substitution-Kinetics, Biomolecular Responses and Multimodal Anticancer Potential of a Dihalide Pd(II) Complex.

This study addresses a novel palladium dihalide complex, cis-[Pd(PCAH)Cl₂] (C1), as a promising anticancer agent. XRD analysis reveals a deformed square planar geometry stabilized by hydrogen bonds and π•••π interactions. The M-Cl bonds in C1 demonstrate susceptibility to nucleophilic substitution by 2,2'-bipyridine (Bpy), with kinetic parameters evaluated using spectrophotometry. Fluorometric and spectrophotometric investigations demonstrate that C1 binds to CT DNA and protein with an avidity of around 105 M-1. The interaction with DNA is multifaceted, employing covalent bonding and intercalation, as supported by viscosity measurements. Fluorescence lifetime experiments illustrate that C1 produces static dampening of BSA fluorescence, implying structural adjustments near the tryptophan residue, further corroborated by spectroscopic analyses. The pair's (BSA and C1) FRET distance has also been computed. In vitro cytotoxicity tests suggest that C1 selectively suppresses the growth of breast carcinoma, MDA-MB-231 with IC50=20±2.64 μM, while showing minimal effects on non-cancerous HEK-293 cells. The mechanism of action includes the creation of ROS, leading to mitochondrial apoptosis, as evidenced by various assays, including annexin-V-FITC/PI labeling. Overall, complex C1 exhibits encouraging promise as a selective anticancer drug with a ROS-triggered apoptotic mechanism, particularly effective against breast carcinoma MDA-MB-231 cells.

Redefining Anthraquinone-based Anticancer Drug Design through Subtle Chemical Modifications.

Anthraquinones are well known for their wide spectrum of pharmacological properties. Anthraquinone antibiotics, such as doxorubicin, daunorubicin, epirubicin, and mitoxantrone, have long been used in the clinical management of various tumors. However, their use is limited due to their toxicity effects, especially cardiomyopathy, despite their pronounced therapeutic effects. In recent years, medicinal chemists have explored the possibility of modifying the anthraquinone ring appended with structurally diverse functionality in order to develop better chemotherapeutic agents with fewer adverse effects. The fused polycyclic structure of anthraquinone offers rigidity, planarity, and aromaticity, which helps in double helix DNA intercalation, disruption of G4 DNA, and inhibition of topoisomerase-II enzyme of cancer cells, making them suitable pharmacophore for anticancer drug discovery. Incorporation of suitable functional groups such as amino, hydroxyl, and their derivatives into anthraquinone rings can improve their interactions with biological targets involved in cancer progression. These subtle structural changes produce newer anthraquinone derivatives with improved anticancer properties, increased potency, selectivity, and reduced toxicity, and can overcome multi-drug resistance. On the other hand, the molecular hybrids of the anthraquinone derivatives have been reported to act on multiple targets in cancer cells, as seen in the case of clinical candidates like alectinib, midostaurin, tucatinib, belinostat, and dacinostat. Molecular hybrid has given a new direction for anticancer drug development, which can produce bifunctional drug candidates with reduced toxicity. This review summarizes different structural modifications that have been made to the anthraquinone ring in the last decade with the aim of bringing out potent yet toxicity-free anticancer agents.

Synthesis and biological evaluation of thiourea-tethered benzodiazepinones as anti-proliferative agents targeting JAK-3 kinase.

Owing to anti-cancer potency of the benzodiazepinone derivatives, the study aims to synthesize a library of thiourea-tethered benzodiazepinone derivatives targeting JAK-3 kinase for anti-breast cancer potency. Test compounds showed favourable in silico interactions with the active site of JAK-3 kinase. Compound 5i demonstrated a significant JAK-3 kinase inhibitory potential of 68.28% and appreciable growth inhibition (72.9%) of MDA-MB-468 (breast cancer cells) as per the anti-proliferative screening done by NCI-USA. In addition, 5i was also found to induce apoptosis moderately by 12.4% in the late apoptosis quadrant and arrested cell cycle at the G2/M phase. The wound healing assay demonstrated the anti-metastatic impact of drug 5i by reducing the migratory potential of MDA-MB-468 cells and was found to be stable within the target protein in the molecular dynamic simulation. All the synthesized compounds exhibited drug-appropriate pharmacokinetic profiles as corroborated by computational ADMET analysis. The study indicates that the synthesized library of benzodiazepinone derivatives is efficacious and compound 5i has emerged as a promising hit candidate, and can be explored further for development of potent JAK-3 kinase inhibitors targeting breast cancer.

Biosynthesis and Characterization of Termites Wings Extract Derived Silver, Zinc, and Silver-Doped Zinc Oxide Nanoparticles for Antioxidant and Anticancer Activity.

Bio-waste-derived nanoparticles (NPs) are gaining attention for their biocompatibility, environmental friendliness, and affordability. This study synthesized silver nanoparticles (AgNPs), zinc oxide nanoparticles (ZnONPs), and silver-doped zinc oxide nanoparticles (Ag-ZnO NPs) using termite wing bio-waste (Odontotermes obesus). The synthesized NPs was Characterization by UV-visible spectroscopy, FTIR, SEM-EDX, XRD, and atomic force microscopy (AFM) confirmed successful biosynthesis and purity. AFM provided 3D profiling of the average sizes of 28.4 nm, 19.6 nm, and 11 nm for AgNPs, ZnONPs, and Ag-ZnO NPs, respectively. Among these three nanoparticles, Ag-ZnO NPs showed superior antioxidant activity in DPPH (86 ± 3.61%), ABTS (76 ± 1.5%), and nitric oxide assays (77 ± 1%). In vitro studies demonstrated their significant antibacterial and anticancer potential against Escherichia coli, Staphylococcus aureus, and HeLa cells, with >80% cell viability reduction at 100 µg/mL. These findings highlight the potential of Ag-ZnO NPs as antioxidants, antibacterial agents, and anticancer agents, warranting further in vivo studies for biomedical applications.

Identification of a Possible Endocannabinoid-Mediated Mechanism of Action of Cetylated Fatty Acids

Some musculoskeletal disorders, including osteoarthritis; arthrosis; post-traumatic injuries; and other inflammatory tendon, joint and muscular afflictions, still represent unmet medical needs. Cetylated fatty acids (CFAs) are key components of widely distributed over-the-counter products, especially for topical use, which are intended to reduce symptoms associated with these conditions. Nevertheless, the mechanism of action of CFAs’ analgesic and anti-inflammatory properties has not yet been clearly established. Endocannabinoids, such as 2-arachidonoylglycerol (2-AG) and anandamide (AEA), are known to produce analgesic and anti-inflammatory effects. These compounds undergo physiological inactivation operated by several enzymes, including monoacylglycerol lipase (MAGL). We herein demonstrate for the first time that the therapeutic effects of CFAs may be attributable, at least in part, to their MAGL inhibition activities, which induce a local increase in analgesic/anti-inflammatory endocannabinoids in close proximity to the site of administration. These findings pave the way for the development of new potent local analgesic agents, whose action is based on an indirect cannabinoid effect.

In Vitro and In Silico Cytotoxic Activity of Isocordoin from Adesmia balsamica Against Cancer Cells

This study investigates the anticancer potential of isocordoin, a prenylated chalcone found in Adesmia balsamica. In vitro assays on colorectal (HT-29), breast (MCF-7) and prostate (PC-3) cancer cell lines, together with a non-cancerous colon cell line (CoN CCD841), revealed that isocordoin is cytotoxic, with PC-3 and MCF-7 cells showing the highest sensitivity. The selectivity index was higher for PC-3 (5.2) than for MCF-7 (3.7) and HT-29 (2.9). Isocordoin induced morphological changes suggestive of apoptosis in tumor cells. Mechanistic studies on HT-29 and MCF-7 lines indicated that isocordoin might possess antioxidant properties while promoting the loss of mitochondrial membrane potential and caspases activation. Molecular docking showed a favorable interaction of isocordoin with caspase-3, which could explain its apoptotic effects. In silico predictions suggest that isocordoin has drug-like properties, including good absorption and permeability to the blood-brain barrier. The presence of the prenyl chain in isocordoin appears crucial for cytotoxic activity, supported by its higher lipophilicity and better interaction with caspase-3 compared to non-prenylated 2′,4′-dihydroxychalcone. Overall, isocordoin demonstrates promising anticancer activity, warranting further investigation as a potential therapeutic agent.

Chromatographic retention assisted in-silico prediction of anticancer potential of glucocorticoids on cancer cell lines.

Chromatographic retention assisted in-silico prediction of anticancer potential of glucocorticoids on cancer cell lines.